GWAS on prolonged gestation (post-term birth): analysis of successive Finnish birth cohorts.

J Med Genet 2018 01 10;55(1):55-63. Epub 2017 Oct 10.

University of Auckland, Auckland, New Zealand.

Background: Gestation is a crucial timepoint in human development. Deviation from a term gestational age correlates with both acute and long-term adverse health effects for the child. Both being born preterm and post-term, that is, having short and long gestational ages, are heritable and influenced by the prenatal and perinatal environment. Despite the obvious heritable component, specific genetic influences underlying differences in gestational age are poorly understood.

Methods: We investigated the genetic architecture of gestational age in 9141 individuals, including 1167 born post-term, across two Northern Finland cohorts born in 1966 or 1986.

Results: Here we identify one globally significant intronic genetic variant within the gene that is associated with prolonged gestation (p=4.85×10). Additional variants that reached suggestive levels of significance were identified within introns at the and genes, and in the upstream (5') intergenic regions of the and genes. The variants near the , , and loci are linked to alterations in gene expression levels (cis-eQTLs). Luciferase assays confirmed the allele specific enhancer activity for the and loci.

Conclusions: Our findings provide the first evidence of a specific genetic influence associated with prolonged gestation. This study forms a foundation for a better understanding of the genetic and long-term health risks faced by induced and post-term individuals. The long-term risks for induced individuals who have a previously overlooked post-term potential may be a major issue for current health providers.

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